TY - JOUR
T1 - Transplantation of immortalized CD34+ and CD34-adipose-derived stem cells improve cardiac function and mitigate systemic pro-inflammatory responses
AU - Kim, Jong Ho
AU - Choi, Seung Cheol
AU - Park, Chi Yeon
AU - Park, Jae Hyoung
AU - Choi, Ji Hyun
AU - Joo, Hyung Joon
AU - Hong, Soon Jun
AU - Lim, Do-Sun
PY - 2016/2/1
Y1 - 2016/2/1
N2 - Adipose-derived stem cells (ADSCs) have the potential to differentiate into various cell lineages and they are easily obtainable from patients, which makes them a promising candidate for cell therapy. However, a drawback is their limited life span during in vitro culture. Therefore, hTERT-immortalized CD34+ and CD34-mouse ADSC lines (mADSCshTERT) tagged with GFP were established. We evaluated the proliferation capacity, multi-differentiation potential, and secretory profiles of CD34+ and CD34-mADSCshTERT in vitro, as well as their effects on cardiac function and systemic inflammation following transplantation into a rat model of acute myocardial infarction (AMI) to assess whether these cells could be used as a novel cell source for regeneration therapy in the cardiovascular field. CD34+ and CD34-mADSCshTERT demonstrated phenotypic characteristics andmulti-differentiation potentials similar to those of primary mADSCs. CD34+ mADSCshTERT exhibited a higher proliferation ability compared to CD34-mADSCshTERT, whereas CD34-mADSCshTERT showed a higher osteogenic differentiation potential compared to CD34+ mADSCshTERT. Primary mADSCs, CD34+, and CD34-mADSCshTERT primarily secreted EGF, TGF-β1, IGF-1, IGF-2, MCP-1, and HGFR. CD34+ mADSCshTERT had higher secretion of VEGF and SDF-1 compared to CD34-mADSCshTERT. IL-6 secretion was severely reduced in both CD34+ and CD34-mADSCshTERT compared to primary mADSCs. Transplantation of CD34+ and CD34-mADSCshTERT significantly improved the left ventricular ejection fraction and reduced infarct size compared to AMI-induced rats after 28 days. At 28 days after transplantation, engraftment of CD34+ and CD34-mADSCshTERT was confirmed by positive Y chromosome staining, and differentiation of CD34+ and CD34-mADSCshTERT into endothelial cells was found in the infarctedmyocardium. Significant decreases were observed in circulating IL-6 levels in CD34+ and CD34-mADSCshTERT groups compared to the AMI-induced control group. Transplantation of CD34-mADSCshTERT significantly reduced circulating MCP-1 levels compared to the AMI control and CD34+ mADSCshTERT groups. GFP-tagged CD34+ and CD34-mADSCshTERT are valuable resources for cell differentiation studies in vitro as well as for regeneration therapy in vivo.
AB - Adipose-derived stem cells (ADSCs) have the potential to differentiate into various cell lineages and they are easily obtainable from patients, which makes them a promising candidate for cell therapy. However, a drawback is their limited life span during in vitro culture. Therefore, hTERT-immortalized CD34+ and CD34-mouse ADSC lines (mADSCshTERT) tagged with GFP were established. We evaluated the proliferation capacity, multi-differentiation potential, and secretory profiles of CD34+ and CD34-mADSCshTERT in vitro, as well as their effects on cardiac function and systemic inflammation following transplantation into a rat model of acute myocardial infarction (AMI) to assess whether these cells could be used as a novel cell source for regeneration therapy in the cardiovascular field. CD34+ and CD34-mADSCshTERT demonstrated phenotypic characteristics andmulti-differentiation potentials similar to those of primary mADSCs. CD34+ mADSCshTERT exhibited a higher proliferation ability compared to CD34-mADSCshTERT, whereas CD34-mADSCshTERT showed a higher osteogenic differentiation potential compared to CD34+ mADSCshTERT. Primary mADSCs, CD34+, and CD34-mADSCshTERT primarily secreted EGF, TGF-β1, IGF-1, IGF-2, MCP-1, and HGFR. CD34+ mADSCshTERT had higher secretion of VEGF and SDF-1 compared to CD34-mADSCshTERT. IL-6 secretion was severely reduced in both CD34+ and CD34-mADSCshTERT compared to primary mADSCs. Transplantation of CD34+ and CD34-mADSCshTERT significantly improved the left ventricular ejection fraction and reduced infarct size compared to AMI-induced rats after 28 days. At 28 days after transplantation, engraftment of CD34+ and CD34-mADSCshTERT was confirmed by positive Y chromosome staining, and differentiation of CD34+ and CD34-mADSCshTERT into endothelial cells was found in the infarctedmyocardium. Significant decreases were observed in circulating IL-6 levels in CD34+ and CD34-mADSCshTERT groups compared to the AMI-induced control group. Transplantation of CD34-mADSCshTERT significantly reduced circulating MCP-1 levels compared to the AMI control and CD34+ mADSCshTERT groups. GFP-tagged CD34+ and CD34-mADSCshTERT are valuable resources for cell differentiation studies in vitro as well as for regeneration therapy in vivo.
UR - http://www.scopus.com/inward/record.url?scp=84959017269&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84959017269&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0147853
DO - 10.1371/journal.pone.0147853
M3 - Article
C2 - 26840069
AN - SCOPUS:84959017269
VL - 11
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 2
M1 - e0147853
ER -